tbuckley/cabot-search huggingface dataset:
Effect of home cook interventions for salt reduction in China: cluster randomised controlled trial
Authors: Xiaochang Zhang, Puhong Zhang, Danyang Shen, Yuan Li, Feng J He, Jixiang Ma, Wei Yan, Yifu Gao, Donghui Jin, Ying Deng, Fangming Guo, Shichun Yan, Jing Song, Graham A MacGregor, Jing Wu
Journal: BMJ (2023)

Abstract Objective To determine the effects of salt reduction interventions designed for home cooks and family members. Design Cluster randomised controlled trial. Setting Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019. Participants 60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families). Interventions Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions. Main outcome measure Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up. Results 1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly. Conclusions The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake. Trial registration Chinese Clinical Trial Registry ChiCTR1800016804.
Authors’ reply to Bray
Authors: Anushka Soni, Youngjoo Kang, Louise Trewern, John Jackman, David McCartney
Journal: BMJ (2023)

We thank Bray for emphasising the fundamental role of psychological factors in chronic pain. 1 2 The definition of pain by the International Association for the Study of Pain has been recently revised from "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage." 3 The updated definition reduces the emphasis of pain needing to be associated with tissue damage, and the updated accompanying notes include "Pain is always a personal experience that is influenced to varying degrees by biological, psychological and social factors," which further embraces the importance of mind-body interactions that, some may argue, have been previously overlooked. 3 Although a detailed exploration of psychological factors was beyond the scope of our brief review, we did mention the bidirectional relationship between psychological factors and chronic pain and encourage further exploration of these key features of chronic pain. 2 We agree that trying to disentangle the physical aspects of pain from psychological drivers is impossible as the two are closely intertwined, and the main focus should be on supporting a person as a whole and not just their physical health needs.We accept that there are flaws in the current approach to the classification of chronic pain, but our aim was to relay contemporary thinking in the field.This was intended as a backdrop for practical advice to promote early identification and effective communication with people who currently have chronic pain, as the quest for further mechanistic understanding of these incredibly debilitating conditions continues.
KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8+ T cells
Authors: Krishnan K. Mahadevan, Kathleen M. McAndrews, Valerie S. LeBleu, Sujuan Yang, Hengyu Lyu, Bingrui Li, Amari M. Sockwell, Michelle L. Kirtley, Sami J. Morse, Barbara A. Moreno Diaz, Michael P. Kim, Ningping Feng, Anastasia M. Lopez, Paola A. Guerrero, Francesca Paradiso, Hikaru Sugimoto, Kent A. Arian, Haoqiang Ying, Yasaman Barekatain, Lakshmi Kavitha Sthanam, Patience J. Kelly, Anirban Maitra, Timothy P. Heffernan, Raghu Kalluri
Journal: Cancer Cell (2023)
Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes
Authors: Jie Wei, Hyon K. Choi, Nicola Dalbeth, Xiaoxiao Li, Changjun Li, Chao Zeng, Guanghua Lei, Yuqing Zhang
Journal: JAMA Network Open (2023)

Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown.
α-Synuclein-carrying astrocytic extracellular vesicles in Parkinson pathogenesis and diagnosis
Authors: Pan Wang, Guoyu Lan, Bin Xu, Zhenwei Yu, Chen Tian, Xia Lei, Wassilios G. Meissner, Tao Feng, Ying Yang, Jing Zhang
Journal: Translational Neurodegeneration (2023)

The accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders.Primary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+ AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism.The number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877.Pathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.
Baseline characteristics of patients enrolled in the <scp>EMPACT‐MI</scp> trial
Authors: Josephine Harrington, Jacob A. Udell, W. Schuyler Jones, Stefan D. Anker, Deepak L. Bhatt, Mark C. Petrie, Knut Robert Andersen, Mikhail Sumin, Isabella Zwiener, Adrian F. Hernandez, Javed Butler
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims Empagliflozin has been shown to reduce the risk of adverse cardiovascular outcomes in patients with type 2 diabetes and in those with heart failure. The impact of empagliflozin in post‐acute myocardial infarction (AMI) patients is unknown. Methods and results The Study to Test the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction (EMPACT‐MI) trial screened 6610 participants with AMI and randomized 6522 to empagliflozin or placebo in addition to standard of care. The median (interquartile) age was 64 (56–71) years and 75.1% of patients were male. Major comorbidities included hypertension (69.1%), type 2 diabetes (31.7%), prior myocardial infarction (13.0%), and atrial fibrillation (10.9%). The majority (74.3%) of patients presented with an ST‐elevation myocardial infarction. Overall, 56.9% of patients had acute signs or symptoms of congestion requiring treatment and 78.3% had left ventricular systolic dysfunction with ejection fraction &lt;45%. Clinical characteristics, including baseline demographics, rates of revascularization, and cardiovascular medications at discharge were largely comparable to recent trials of the post‐AMI population. Conclusion The EMPACT‐MI trial will establish the benefit and risks of empagliflozin treatment in patients with AMI.
BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Liwei Zhao, Peng Liu, Misha Mao, Shuai Zhang, Camille Bigenwald, Charles-Antoine Dutertre, Christian H.K. Lehmann, Hui Pan, Nicolas Paulhan, Lukas Amon, Aitziber Buqué, Takahiro Yamazaki, Lorenzo Galluzzi, Benoit Kloeckner, Aymeric Silvin, Yuhong Pan, Hui Chen, Ai-Ling Tian, Pierre Ly, Diana Dudziak, Laurence Zitvogel, Oliver Kepp, Guido Kroemer
Journal: Cancer Discovery (2023)

Abstract We developed a phenotypic screening platform for the functional exploration of dendritic cells (DC). Here, we report a genome-wide CRISPR screen that revealed BCL2 as an endogenous inhibitor of DC function. Knockout of BCL2 enhanced DC antigen presentation and activation as well as the capacity of DCs to control tumors and to synergize with PD-1 blockade. The pharmacologic BCL2 inhibitors venetoclax and navitoclax phenocopied these effects and caused a cDC1-dependent regression of orthotopic lung cancers and fibrosarcomas. Thus, solid tumors failed to respond to BCL2 inhibition in mice constitutively devoid of cDC1, and this was reversed by the infusion of DCs. Moreover, cDC1 depletion reduced the therapeutic efficacy of BCL2 inhibitors alone or in combination with PD-1 blockade and treatment with venetoclax caused cDC1 activation, both in mice and in patients. In conclusion, genetic and pharmacologic BCL2 inhibition unveils a DC-specific immune checkpoint that restrains tumor immunosurveillance. Significance: BCL2 inhibition improves the capacity of DCs to stimulate anticancer immunity and restrain cancer growth in an immunocompetent context but not in mice lacking cDC1 or mature T cells. This study indicates that BCL2 blockade can be used to sensitize solid cancers to PD-1/PD-L1–targeting immunotherapy. This article is featured in Selected Articles from This Issue, p. 2293
Alert Timing in Sepsis Prediction Models—An Opportunity to Tailor Interventions
Authors: Emily A. Balczewski, Patrick G. Lyons, Karandeep Singh
Journal: JAMA Network Open (2023)

Adam R. Schertz, MD, MS; Kristin M. Lenoir, MPH; Alain G. Bertoni, MD, MPH; Beverly J. Levine, PhD; Morgana Mongraw-Chaffin, PhD; Karl W. Thomas, MD
Antioxidant peptides, the guardian of life from oxidative stress
Authors: Yiyun Zhu, Kang Wang, Xinyi Jia, Caili Fu, Haining Yu, Yipeng Wang
Journal: Medicinal Research Reviews (2023)

Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro-oxidants, thus showing great potential in the treatment of oxidative stress-related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress-related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.
Q&amp;A: Olena Yefimenko on Cancer Care, Research in Ukraine
Journal: Cancer Discovery (2023)

Olena Yefimenko, MD, director of the National Cancer Institute of Ukraine, talks about the challenges to care, treatment, and research-and how she and her colleagues would like the Ukrainian cancer enterprise to grow and evolve in the years to come. Portions of the interview can also be viewed at https://vimeo.com/850195825.
Long-Term Incidence of Ischemic Stroke After Transient Ischemic Attack: A Nationwide Study From 2014 to 2020
Authors: Naja Emborg Vinding, Jawad H. Butt, Marie Dam Lauridsen, Søren Lund Kristensen, Søren Paaske Johnsen, Johanna Krøll, Peter L. Graversen, Christina Kruuse, Christian Torp-Pedersen, Lars Køber, Emil L. Fosbøl
Journal: Circulation (2023)

The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies.
Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level
Authors: Anais Joachim, Rudy Aussel, Léna Gélard, Fanghui Zhang, Daiki Mori, Claude Grégoire, Sergio Villazala Merino, Mauro Gaya, Yinming Liang, Marie Malissen, Bernard Malissen
Journal: The Journal of Experimental Medicine (2023)

Mice with a loss-of-function mutation in the LAT adaptor (LatY136F) develop an autoimmune and type 2 inflammatory disorder called defective LAT signalosome pathology (DLSP). We analyzed via single-cell omics the trajectory leading to LatY136F DLSP and the underlying CD4+ T cell diversification. T follicular helper cells, CD4+ cytotoxic T cells, activated B cells, and plasma cells were found in LatY136F spleen and lung. Such cell constellation entailed all the cell types causative of human IgG4-related disease (IgG4-RD), an autoimmune and inflammatory condition with LatY136F DLSP-like histopathological manifestations. Most previously described T cell-mediated autoimmune manifestations require persistent TCR input. In contrast, following their first engagement by self-antigens, the autoreactive TCR expressed by LatY136F CD4+ T cells hand over their central role in T cell activation to CD28 costimulatory molecules. As a result, all subsequent LatY136F DLSP manifestations, including the production of autoantibodies, solely rely on CD28 engagement. Our findings elucidate the etiology of the LatY136F DLSP and qualify it as a model of IgG4-RD.
The COVID-19 Pandemic and Associated Inequities in Acute Myocardial Infarction Treatment and Outcomes
Authors: Laurent G. Glance, Karen E. Joynt Maddox, Jingjing Shang, Patricia W. Stone, Stewart J. Lustik, Peter W. Knight, Andrew W. Dick
Journal: JAMA Network Open (2023)

The COVID-19 pandemic disrupted usual care for emergent conditions, such as acute myocardial infarction (AMI). Understanding whether Black and Hispanic individuals experiencing AMI had greater increases in poor outcomes compared with White individuals during the pandemic has important equity implications.To investigate whether the COVID-19 pandemic was associated with increased disparities in treatment and outcomes among Medicare patients hospitalized with AMI.This cross-sectional study used Medicare data for patients hospitalized with AMI between January 2016 and November 2020. Patients were categorized as Hispanic, non-Hispanic Black, and non-Hispanic White. The association between race and ethnicity and outcomes as a function of the proportion of hospitalized patients with COVID-19 was evaluated using interrupted time series. Data were analyzed from October 2022 to June 2023.The main exposure was a hospital's proportion of hospitalized patients with COVID-19 on a weekly basis as a proxy for care disruption during the pandemic.Revascularization, 30-day mortality, 30-day readmission, and nonhome discharges.A total of 1 319 273 admissions for AMI (579 817 females [44.0%]; 122 972 Black [9.3%], 117 668 Hispanic [8.9%], and 1 078 633 White [81.8%]; mean [SD] age, 77 [8.4] years) were included. For patients with non-ST segment elevation MI (NSTEMI) overall, the adjusted odds of mortality and nonhome discharges increased by 51% (adjusted odds ratio [aOR], 1.51; 95% CI, 1.29-1.76; P < .001) and 32% (aOR, 1.32; 95% CI, 1.15-1.52; P < .001), respectively, and the odds of revascularization decreased by 27% (aOR, 0.73; 95% CI, 0.64-0.83; P < .001) among patients hospitalized during weeks with a high hospital COVID-19 burden (>30%) vs patients hospitalized prior to the pandemic. Black individuals with NSTEMI experienced a clinically insignificant 7% greater increase in the odds of mortality (aOR, 1.07; 95% CI, 1.00-1.15; P = .04) for each 10% increase in the COVID-19 hospital burden but no increases in readmissions or nonhome discharges or reductions in revascularization rates compared with White individuals. There were no differential increases in adverse outcomes among Hispanic compared with White patients with NSTEMI based on hospital COVID-19 burden. Increases in hospital COVID-19 burden were not associated with changes in outcomes or the use of revascularization in STEMI overall or by racial or ethnic group.This study found that while hospital COVID-19 burden was associated with worse treatment and outcomes for NSTEMI, race and ethnicity-associated inequities did not increase significantly during the pandemic. These findings suggest the need for additional efforts to mitigate outcomes associated with the COVID-19 pandemic for patients admitted with AMI when the hospital COVID-19 burden is substantially increased.
Ocular Comorbidities Contributing to Death in the US
Authors: Ryan S. Huang, Andrew Mihalache, Marko M. Popovic, Peter J. Kertes, David T. Wong, Rajeev H. Muni
Journal: JAMA Network Open (2023)

This cross-sectional study estimates the prevalence of ocular comorbidities contributing to death in the US, stratified by age, sex, and race and ethnicity.
Statistical normalization methods in microbiome data with application to microbiome cancer research
Authors: Yinglin Xia
Journal: Gut Microbes (2023)

Mounting evidence has shown that gut microbiome is associated with various cancers, including gastrointestinal (GI) tract and non-GI tract cancers. But microbiome data have unique characteristics and pose major challenges when using standard statistical methods causing results to be invalid or misleading. Thus, to analyze microbiome data, it not only needs appropriate statistical methods, but also requires microbiome data to be normalized prior to statistical analysis. Here, we first describe the unique characteristics of microbiome data and the challenges in analyzing them (Section 2). Then, we provide an overall review on the available normalization methods of 16S rRNA and shotgun metagenomic data along with examples of their applications in microbiome cancer research (Section 3). In Section 4, we comprehensively investigate how the normalization methods of 16S rRNA and shotgun metagenomic data are evaluated. Finally, we summarize and conclude with remarks on statistical normalization methods (Section 5). Altogether, this review aims to provide a broad and comprehensive view and remarks on the promises and challenges of the statistical normalization methods in microbiome data with microbiome cancer research examples.
Surface-tethered ROS-responsive micelle backpacks for boosting mesenchymal stem cell vitality and modulating inflammation in ischemic stroke treatment
Authors: Yang You, Yipu Liu, Chuchu Ma, Jianpei Xu, Laozhi Xie, Shiqiang Tong, Yinzhe Sun, Fenfen Ma, Yukun Huang, Junbin Liu, Wenze Xiao, Chengxiang Dai, Suke Li, Jigang Lei, Qiyong Mei, Xiaoling Gao, Jun Chen
Journal: Journal of Controlled Release (2023)
The Architecture of Metabolic Networks Constrains the Evolution of Microbial Resource Hierarchies
Authors: Sotaro Takano, Jean C C Vila, Ryo Miyazaki, Álvaro Sánchez, Djordje Bajić
Journal: Molecular Biology and Evolution (2023)

Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here, we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability, and ecology.